Sugar & Antibiotics

A couple of interesting stories have come to my attention lately. Despite my efforts to get them across on Twitter, they are still not quite getting the attention I think they deserve, so I’m going to recite them here.

These stories are on the role of sugar and the role of antibiotics in human health. First I’ll start with the one that is more solid, the case of sugar. It’s essentially accepted doctrine that sugar is harmful to health. This ranges from any sugar at all to “excessive” consumption of sugar. Indeed, it’s accepted in many circles that sugar is behind the rise in obesity rates. There’s only one problem: there isn’t actually any good evidence for this.

Let me repeat a point, a point I will keep repeating until it sinks in: uncontrolled correlational studies do not count as evidence.

With that out of the way, let review an interesting post by Anne Buchanan. (Yes, that one. Before anyone makes the accusation, yes, I am well aware of Buchanan’s and crew’s heredity denial. But the expression “even a broken clock…” is a key bit of wisdom to keep in mind. I judge arguments, not people, and so should you.)

The search for magic health bullets, or the Single Evil goes on unabated, despite a steady record of essential failure. Is that fair? Well, we’ve got decades of very extensive, expensive, and expansively technical studies of some questions of major public health relevance — and little to show for it.

As a new example, after a two-year effort to connect the dots between between sugar and disease, the World Health Organization, whose large professional research staff should know how to do that, believes it has done so, and now recommends we all reduce our sugar intake to 10% of our diet, or better yet, 5%. That’s 12 or fewer tablespoons of sugar a day.

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To answer that question, the WHO commissioned a meta-analysis, that is, a single combined analysis of all pertinent previous cohort studies of the effects of sugar on obesity, which was published last month in the British Medical Journal by Morenga et al.

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That is, people in these studies were either asked to add or subtract sugary foods and drinks from their diet, but change nothing else, or they were asked to subtract sugar and substitute it with a different carbohydrate. Presumably the latter was to control for the effect of simply adding or subtracting calories of any sort, though this isn’t clear in the paper.

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From these 30 trials and 38 prospective cohort studies, what do they conclude? Well, of the 30 trials, five studies measured the effect of reducing dietary sugars. To quote the authors of the WHO commissioned BMJ paper, “Reduction in dietary sugars intake was associated with significantly reduced weight (-0.80 kg (95% confidence interval -1.21 to -0.39); P lt 0.001) at the end of the intervention period by comparison with no reduction or an increase in sugars intake.”

So, five studies report statistically ‘significant’ weight loss with reduction in sugar intake. But what are we talking about here? Well, an average decrease of less than 2 pounds, or at most 2 1/2 pounds, with variation around that. This may be ‘statistically significant’, but all I can say is that if I lost 2 pounds I wouldn’t think it important enough to tell my mother about, never mind publish it. And, only one of the studies, participants were asked to substitute low sugar foods for the high sugar foods they were eliminating. So, one study tried to test the effect of eliminating sugar, but not changing caloric intake, but the others did not.

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So, after all of this effort, on a subject that has been widely trumpeted as well-known, is sugar bad for us? Maybe, but we don’t know it from this study. All the studies included in the meta-analysis are based on methods of assessing food intake that are themselves questionable. Dietary recall, the method used in the trials, and food frequency questionnaires used in the cohort studies, or indeed just about any other method of dietary assessment, are notoriously inaccurate measures of what we eat. And, the amount of weight gain reported to be due to sugar consumption is perhaps statistically significant, but with respect to the dangers associated with obesity, it’s trivial.

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All of this is predicated on the assumption that weight gain is unhealthy. Or leads to ill health. The WHO paper didn’t address the strength of the evidence for this. Nor did they show any evidence to suggest that sugar contributes to ill health, or even weight gain, any more than any other food. When speculating on how sugar could be associated with weight gain, the authors write, “The most obvious mechanism by which increasing sugars might promote weight gain is by increasing energy consumption to an extent that exceeds energy output and distorts energy balance.” That is, people who gain weight consume more of anything than they burn, as the isoenergetic studies suggest. By this logic, eliminating milk or eggs or meat and not replacing them would cause weight loss, too.

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Sugar consumption is much less unambiguously associated with tooth decay. Or at least I thought so, and it seemed something ‘everybody knows’…..until I read the review commissioned by the WHO, a paper in the Journal of Dental Research, the foundation for the WHO recommendation that sugar consumption should be less than 5% of our diet.

From 5,990 papers identified, 55 studies were eligible – 3 intervention, 8 cohort, 20 population, and 24 cross-sectional. Data variability limited meta-analysis. Of the studies, 42 out of 50 of those in children and 5 out of 5 in adults reported at least one positive association between sugars and caries. There is evidence of moderate quality showing that caries is lower when free-sugars intake is < 10% E. With the < 5% E cut-off, a significant relationship was observed, but the evidence was judged to be of very low quality. The findings are relevant to minimizing caries risk throughout the life course.

The evidence for an association is judged to be ‘moderate’ or ‘of very low quality.’ This largely reflects the fact that most studies didn’t ask the question the WHO was interested in — is there a threshold amount of sugar that is highly associated with cavities? Still, the studies do show an association, even if confounders like socioeconomic status might be problems.

Buchanan seems to be channeling many criticisms I have made, as I did in a Twitter discussion I once had with John Durant. The commonly held belief that sugar per se leads to ill-health – even the most basic (and commonly accepted) link in the case of tooth decay – isn’t based on any good evidence. That sugar is the cause of the rise in obesity is also commonly believed, but is not substantiated.

Notice that sugar is notoriously absent from Greg Cochran’s discussion of health problems stemming from poor adaptation to evolutionary novel foodstuffs (Death by Chocolate | West Hunter). Odds are people looking at sugar are looking in the wrong place.

IF you walk into a farm-supply store today, you’re likely to find a bag of antibiotic powder that claims to boost the growth of poultry and livestock. That’s because decades of agricultural research has shown that antibiotics seem to flip a switch in young animals’ bodies, helping them pack on pounds. Manufacturers brag about the miraculous effects of feeding antibiotics to chicks and nursing calves. Dusty agricultural journals attest to the ways in which the drugs can act like a kind of superfood to produce cheap meat.

Now, of course, I am a huge critic of generalizing from animals to humans. However, the article does mention that at least one human trial was conducted:

Researchers also tried this out in a study of Navy recruits. “Nutritional effects of antibiotics have been noted for some time” in farm animals, the authors of the 1954 study wrote. But “to date there have been few studies of the nutritional effects in humans, and what little evidence is available is largely concerned with young children. The present report seems of interest, therefore, because of the results obtained in a controlled observation of several hundred young American males.” The Navy men who took a dose of antibiotics every morning for seven weeks gained more weight, on average, than the control group.

Unfortunately, time is often lacking for me. I suppose if I dug more deeply (which I may still do at some point), I could turn up evidence that could more definitively establish, yay or nay, on the role of antibiotics in human obesity. However, for now, I will put this out there as an idea that needs further attention. Attempts to nail down the cause of the rise in obesity have been infamously unsuccessful. Part of the investigation has been handicapped by the fact that diet and exercise are assumed to be the ultimate causes. This is far from clear at the moment. I don’t know if antibiotics will hold up as a potential cause either. I am not claiming to know the method that antibiotics plays this role (whether they, for example, alter the composition of the gut microbiome). However, I do believe this is worth closer attention.

For sugar and antibiotics, an interesting irony exists. One is commonly believed to be behind poor health and obesity, and in fact may not be. The other an agent that has legitimately been instrumental in improving human health, but may have the side effect of fattening us up. The laser-like focus on lifestyle has served to make us more paranoid about health, but what do we have to show for it? Not much, as previously discussed in my posts on the matter (Trans Fat Hysteria and the Mystery of Heart Disease and Even George W. Bush Has Heart Disease). Of course, we are likely to run into trouble with antibiotics soon anyway (see Imagining the Post-Antibiotics Future)…

…but that’s a whole ‘nother problem entirely. It would be helpful if modern research would break free of its sociological determinism and hence do a better job at finding what truly ails us.

EDIT: As an example of a worthless correlational study, I present this meta analysis published in the journal PLOS ONE of observational studies looking at birth by Cesarian section versus vaginal delivery and later obesity. It found that babies delivered by C-section were more likely to be obese as adults. It’s an example of the best and baddest of correlational studies. Did even one of those studies control for parental obesity? Doesn’t look that way. Did any of them try to look at differences between siblings where one was delivered vaginally and the other by C-section? Nope. It is a completely worthless study; all it shows is that obese people may be more prone to give birth via C-section – with no idea of the true causes or best correlates at least. Yet, it is being circulated as if it was definitive proof. Give me a break.

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28 Comments

Great post. I keep meaning to make a donation again, let me sort that out this week. Hope fatherhood is not wearing you out.
” I am not claiming to know the method that antibiotics plays this role (whether they, for example, alter the composition of the gut microbiome..”
Well antibiotics are known to kill a lot of the beneficial bacteria in the gut in addition to treating a bacterial infection. Altering the microbiota alters carbohydrate metabolism (as well as often causing diarrhea); I assume this is what causes the weight gain.
If altering intestinal microbiota alters carbohydrate metabolism, then antibiotics aren’t the only possible culprits for obesity, there are many others. Long term contraceptive pill use apparently alters the intestinal microbiome (in addition to the vaginal microbiome) for instance.
The rise in obesity, neurodevelopmental disorders, autoimmune diseases and cancers all run in parallel with the rise in antibiotic use. It certainly wouldn’t surprise me if it turns out to be a major cause. We’ll wait and see.

My dentist tells me that sugar and sugary drinks aren’t really that bad, as long as they’re washed down so the sugar doesn’t stick to the teeth. Diet sodas can be almost as bad as regular, because many sodas have lots of phosphoric acid. He recommends eating chocolate without nuts or fruits, because the chocolate will melt and come off your teeth while the fruits and nuts will get stuck between your teeth and feed the decay bacteria.

I don’t know if he has any studies backing up his opinion, but he does have a more sophisticated, yet still plausible, causal mechanism than “sugar feeds decay bacteria, rots teeth”.

There’s also the problem of what advice to give patients depending how smart/educated they are, and how likely they are to follow through on it – lots of advice seems to be over-simplified to make it something which a barely literate high-school dropout can remember.

Sugar makes food taste better. People are probably inclined to eat more of everything when it tastes better.

Different sugars are metabolized differently. Fructose, for example, is metabolized in the liver, while glucose is used straight. This is just chem/bio. The metabolism of fructose may require the use of other nutrients that are found in normal foods, but refinement of fructose leads to more fructose in food than available nutrients to properly digest it. See, eg:

My suspicion is that good taste + nutrient imbalance will lead people to eat more to get the nutrients they need. The general advice of “eat less!” is then counterproductive.

I don’t mean to single out fructose, I just happened to have come across some details about it. I don’t know whether or not other forms of sugar have other potential metabolism issues when refined, but different metabolic paths would make studies of “sugar” intake potentially completely useless.

I suspect that the sugar itself doesn’t cause tooth decay (sugar is used as a preservative in jams, after all…) but the nutrient imbalance leads the body to dip into its mineral stores, weakening bones and making them more susceptible to decay.

Hispanic immigrants in ”America” have higher expectance of life than whites because they came to ”traditional amerindian cultures” and their biology more adapted to their cultural diet.
Fat people necessarily doesn’t not indicate ”less health”, they are only the variation of human bodies. Some studies indicated that fat people tend to be more fertile than skinny people. Obviously there some advantages to fat people to exist today.
The most important ratio there in health is ”biology and lifestyle adapted to diet”.
But the ”environment” causes are in true only this ratio, and it is biologic and genetic.

Maybe people who are over weight and who eat too much sugar when asked to cut down on sugar simply eat more of anything they can get their hands on.

which could explain why they only lost 2 pounds

over eaters, people who can not control their need to “inhale” food will eat too much of anything. Sugar is probably the more pleasing food to indulge in but those people will probably over eat salty or greasy food if sugary food are unavailable , heck they will probably over eat bland tasting food if that is the only thing available

kind of like some drug addicts will go as far as inhale gasoline or spray paint just to get the high they can not live without.

Jay, you’re completely correct that these correlational studies are mostly garbage. Nutritional studies are some of the worst offenders. The breastfeeding-IQ studies come to mind as well–you’d think the original studies finding the link between breastfeeding and IQ would have noticed certain important differences between the populations who breastfeed and those who don’t.

Anyway, we all know that diet affects health–humans need a complex mix of nutrients, and an all-sugar diet would kill you. American diets have changed dramatically over the last 100 years, and it would be no surprise if these massive changes have had significant health effects.

I’m not familiar with all of the evidence related to sugar, but it is at least plausible that adding sugar to foods is generally bad for people. Consider that cheap added sugar is a relatively recent technological change, so we haven’t had much time to adapt to mass quantities of it. It seems reasonable enough that adding a lot of appealing extra calories to food without adding all of the other nutrients we need may just result in many of us eating more calories just to get the same quantities of the other stuff.

Aside from correlational studies, I know there are reports of health declines when Western foods were introduced in various places–increases in weight and tooth decay in particular. Sugar seems likely to be at least part of the problem.

Cochran didn’t mention sugar because sugar isn’t a plant or other food found only in specific regions of the world. “Sugar” refers to a variety of different chemicals found in many different foods and variously removed, refined, modified, or concentrated in modern foods. No one is allergic to “sugar”. We’re all adapted to “sugar” because glucose is the basic stuff cells use. (Someone more knowledgeable than me can interject about high-fat ketone based diets.)

That doesn’t mean anything, good or bad, about the body’s ability to tolerate refined or concentrated sugars, anymore than it means anything about low or high fat diets, high or low salt, etc. It doesn’t mean anything at all on the subject of sugar, really.

No duh. I was responding directly to “Notice that sugar is notoriously absent from Greg Cochran’s discussion of health problems stemming from poor adaptation to evolutionary novel foodstuffs (Death by Chocolate | West Hunter).” and “Is anyone clicking on the link to Cochran’s post?”

Cochran doesn’t discuss sugar because sugar’s not a food. It’s a component of food, like calcium or lycopene. Just because it’s not discussed in a post that’s about a different class of foodstuffs is completely irrelevant to whether or not it’s good for you.

Maximo Macaroni / Mar 10 2014 11:41 AM

Maybe we have a lot of data we’re just not looking at. For instance, sugar rationing in World War II created a huge experimental database of civilians who ate much less sugar for some years – rationing didn’t stop right after the war. Now, soldiers may have been able to get more sugar in the same years. Lots of medical data should be available for soldiers, probably less for civilians. Why can’t those populations be compared to each other and to themselves before the war and after rationing? Has this been done? Or are there too many confounding factors? For instance, death rates among soldiers would be expected to be higher.

Well, considering that my blood sugar spikes and then crashes in ways that leave me feeling extremely shitty anytime I eat sugars in large quantities, (I’ve even had the unpleasant experience of thinking something was low-sugar until after I ate it, crashed, and then re-read the packaging, so it’s not just confirmation bias) I’d think that society had gone off its rocker and was completely nuts. At best, sugar is harmless to some people, but for other people it is absolutely a health issue.

Sisyphean / Mar 12 2014 10:43 AM

I would stab people with large knives made of poured sugar and then cackle with obscene laughter until they carted me off. Is that what you were looking for?

chrisdavies09 / Mar 11 2014 6:23 PM

“it’s accepted in many circles that sugar is behind the rise in obesity rates. There’s only one problem: there isn’t actually any good evidence for this.”

I think that you are right to point out the shortfalls in studies which are cited as evidence for sugar being behind the rise in obesity rates.

You talk about sugar and antibiotics in the same post. Long term antibiotic use can cause an overgrowth of candida albicans in the gastrointestinal tract (antibiotic candidiasis). High sugar consumption can also lead to candidiasis. Candida albicans feeds off sugar. An overgrowth of candida creates a craving for sugar in the host. This could be a plausible mechanism for a rise in obesity, with widespread antibiotic use, widespread high sugar/refined carohydrate consumption, and widespread contraceptive pill use in the modern era all contributing to it.

I personally can’t agree with you that there is no good evidence for sugar being behind the rise in obesity rates. You seem reasonably convinced that antibiotic use could be a contributory factor towards the rise in obesity. However there already exists quite convincing evidence that sugar could work by the same mechanism.

That is a great comment but candida albicans overgrowth in the digestive tract which is a problem I have had for 18 years, in fact since I became plagued with CFS/Chronic Fatigue Syndrome is unfortunately something most medical experts do not even believe is a real problem ( just as most do not believe CFS is real )

I am not cured now but I am MUCH better and I only got better once I began cutting sugary food almost completely from my diet

everything else that I was told to do by health professionals or that I read in books or online was useless , cutting sugar was the almost miracle sure for me ( almost as I am still not 100 % cured and I do have occasional flare ups of CFS symptoms )

if I cheat and eat sugary food, within half an hour my belly becomes insanely bloated, and then for the next two or three days I feel sluggish and and very tired, yet all I want to eat is sugary food

I crave it more when I have those weird symptoms

In the first few years of my condition I had not connected the dots about sugar and candida albicans and CFS …and I gained about 30 pounds because I craved sugar like never before but was also hungry all the time for antyhing not only sugar

After years of that and after having read thousands and thousands of hours of health material ( I have no training in anything related to health ) I came to the conclusion that a lot of over weight people probably have my problem and they don;t know it ( their fatigue symptoms might be less pronounced ) they are always hungry because of the candida albicans

ok my comment is already too long, I will stop here

panjoomby / Mar 11 2014 8:04 PM

no twin studies? Randomized Controlled Trials? yeast? food monoculture? cattle antibiotics leaking into humans? no evidence for differential metabolism of sugar? i’m happy that i don’t care about diet – the media care – sells papers, etc. you’re right to argue with durant – the paleo-diet stuff is ridiculous – marlene zuk does a good job of explaining why from an evolutionary perspective in her book “paleofantasy” 🙂

they forgot to consider the hypothesis that fat people tend to be dumber – instead they hint that obesity causes poor grades (at least they didn’t say that prettier girls are given higher grades simply for being pretty:)

The CS/Obesity study is truly awful. Obstetricians and epidemiologistst already know that CS/VB outcomes can’t be compared in this crude fashion because CS/VB decisions are not random. In fact their are two distinct groups of people who have CS, firstly mothers with problems and secondly high income/professional women who have elective CS. If you compare CS/VB rates in Aus/NZ, which should be very similar, a large difference emerges due to the relative number of babies delivered by midwives vs obstetricians. In Aus, which has the higher CS rate, all the women who had CS in NZ would also be having it in Aus, but a large number of women with different characteristics are also having CS. The only overlap between these groups is that their is a correlation between maternal age and CS rate in both groups. Meta-analysis which fails to either of these factors into account is problematic.

It is also true that we already know that a strong correlation exists between maternal weight, and not surprisingly maternal blood pressure, and CS rates. So if maternal obesity has either an environmental or genetic effect on children’s obesity we would expect to see a correlation. In fact the meta analysis actually mentions a study that found no effect, after controlling for maternal height & weight, but then goes on to ignore it. In general all the confounding factors for that exist for obesity/mortality correlations, such as smoking, poverty, general poor health etc, also independently affect CS rates. The meta-analysis mentions some of these things as potential confounding factors but seems to suggest we have found this exciting correlation, it perhaps just maybe could be explained partially by these other things, but it’s much more likely our crude result is meaningful and therefore CS is bad, (an opinion they no doubt already held). Whereas in fact it is much more likely that the result is meaningless. All these problems would be bad enough in a single study but much more weight is placed on meta-analyses, with good reason, and so the problems seem even more egregious. This is why you have used it as an example. Perhaps a, properly randomized, longditudinal study of the weight/BMI of children born to normal weight mothers who have elective CS could discover whether or not the claims of the meta-analysis have any merit.

It can be difficult, in general, to compare sibling outcomes for CS/VB because one CS inevitably follows another, because having a CS may have independent effects on future VBs and also because of maternal age differences in CS rates. But none of these problems is insurmountable with proper experimental design.

When something is well understood it is simple. Weight gain is obviously like Global Warming – partly understood but there is some obvious missing pieces.

Experts have a vested interest in their expertise so they like to pretend that there is less ignorance in the world than there really is. For example John Hawks had a link recently to an article that pointed out that chimpanzees in labs are also undergoing obesity problems. These animals eat a controlled diet (Purina Monkey Chow?) and the proportions are controlled. Yet they are now getting fat. So are other lab animals.

If anyone wants to impress me with their expertise first explain to me why the monkeys are getting chunky. Then you might tell me why the Milankovich cycles changed their period rate 700,000 years ago.

Regarding antibiotics and weight gain, farmers use them to add muscle mass, not fat. Fat animals are graded down and earn less than those with more meat on them. See: ‘There has been a developing controversy surrounding the use of antibiotics as growth promoters for food animals. These drugs are used at low doses in animal feeds and are considered to improve the quality of the product, with a lower percentage of fat and a higher protein content in the meat.’http://www.fao.org/docrep/ARTICLE/AGRIPPA/555_EN.HTM

Nobody mentioned gut biota other than the pathological candida. The precise mixture and heredity of the commensal bacteria in the gut is bound to have a huge effect on digestion and nutrient absorption. Diet will change the proportions of different strains. Antibiotics will have even bigger effects.

I’d like to see more research on the effectiveness of nuking the gut biota of obese patients with antibiotics then doing a stool transplant.

Here’s an overview of some results: “…95% immediate cure in patients infected with antibiotic resistant strains of Clostridium difficile…. reports of cures for some cases of ulcerative colitis, chronic constipation, Parkinson’s disease and various auto-immune conditions such as Multiple Sclerosis, Rheumatoid Arthritis, Diabetes Type 1 and Chronic Fatigue…. It has been shown that the gut flora of obese and lean individuals is markedly different. Microflora of obese individuals release nutrients in food that remain undigested in lean individuals. Lean mice who receive transplanted feces from obese mice, cause the lean mice to put on weight!”

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